GUC2A_HUMAN
ID GUC2A_HUMAN Reviewed; 115 AA.
AC Q02747;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Guanylin;
DE AltName: Full=Guanylate cyclase activator 2A;
DE AltName: Full=Guanylate cyclase-activating protein 1;
DE AltName: Full=Guanylate cyclase-activating protein I;
DE Short=GCAP-I;
DE Contains:
DE RecName: Full=HMW-guanylin;
DE Contains:
DE RecName: Full=Guanylin;
DE Flags: Precursor;
GN Name=GUCA2A; Synonyms=GUCA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PHE-7.
RC TISSUE=Duodenum;
RX PubMed=1327879; DOI=10.1016/0014-5793(92)81387-2;
RA Wiegand R.C., Kato J., Huang M.D., Fok K.F., Kachur J.F., Currie M.G.;
RT "Human guanylin: cDNA isolation, structure, and activity.";
RL FEBS Lett. 311:150-154(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT PHE-7.
RC TISSUE=Ileum;
RX PubMed=1409606; DOI=10.1073/pnas.89.19.9089;
RA de Sauvage F.J., Keshav S., Kuang W.J., Gillett N., Henzel W.,
RA Goeddel D.V.;
RT "Precursor structure, expression, and tissue distribution of human
RT guanylin.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9089-9093(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PHE-7.
RC TISSUE=Placenta;
RX PubMed=7892222; DOI=10.1073/pnas.92.6.2046;
RA Hill O., Kuhn M., Zucht H.-D., Cetin Y., Kulaksiz H., Adermann K.,
RA Klock G., Rechkemmer G., Forssmann W.-G., Maegert H.-J.;
RT "Analysis of the human guanylin gene and the processing and cellular
RT localization of the peptide.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:2046-2050(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP PROTEIN SEQUENCE OF 22-68.
RX PubMed=8095028; DOI=10.1016/0014-5793(93)80022-m;
RA Kuhn M., Raida M., Adermann K., Schulz-Knappe P., Gerzer R., Heim J.-M.,
RA Forssmann W.-G.;
RT "The circulating bioactive form of human guanylin is a high molecular
RT weight peptide (10.3 kDa).";
RL FEBS Lett. 318:205-209(1993).
RN [6]
RP STRUCTURE BY NMR OF 101-115.
RX PubMed=7947768; DOI=10.1021/bi00250a010;
RA Skelton N.J., Garcia K.C., Goeddel D.V., Quan C., Burnier J.P.;
RT "Determination of the solution structure of the peptide hormone guanylin:
RT observation of a novel form of topological stereoisomerism.";
RL Biochemistry 33:13581-13592(1994).
RN [7]
RP STRUCTURE BY NMR OF 22-115, AND DISULFIDE BONDS.
RX PubMed=12707255; DOI=10.1074/jbc.m300370200;
RA Lauber T., Neudecker P., Rosch P., Marx U.C.;
RT "Solution structure of human proguanylin: the role of a hormone
RT prosequence.";
RL J. Biol. Chem. 278:24118-24124(2003).
CC -!- FUNCTION: Endogenous activator of intestinal guanylate cyclase. It
CC stimulates this enzyme through the same receptor binding region as the
CC heat-stable enterotoxins.
CC -!- INTERACTION:
CC Q02747; Q12797-6: ASPH; NbExp=3; IntAct=EBI-12244272, EBI-12092171;
CC Q02747; O15552: FFAR2; NbExp=3; IntAct=EBI-12244272, EBI-2833872;
CC Q02747; P48165: GJA8; NbExp=3; IntAct=EBI-12244272, EBI-17458373;
CC Q02747; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-12244272, EBI-712073;
CC Q02747; O14524-2: NEMP1; NbExp=3; IntAct=EBI-12244272, EBI-10969203;
CC Q02747; O43765: SGTA; NbExp=8; IntAct=EBI-12244272, EBI-347996;
CC Q02747; O95436-2: SLC34A2; NbExp=3; IntAct=EBI-12244272, EBI-12811757;
CC Q02747; Q7Z7N9: TMEM179B; NbExp=3; IntAct=EBI-12244272, EBI-11724423;
CC Q02747; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-12244272, EBI-10982110;
CC Q02747; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-12244272, EBI-2548832;
CC Q02747; Q15629: TRAM1; NbExp=3; IntAct=EBI-12244272, EBI-1788852;
CC Q02747; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-12244272, EBI-741480;
CC Q02747; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-12244272, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Highly expressed in ileum and colon. Found in
CC plasma.
CC -!- SIMILARITY: Belongs to the guanylin family. {ECO:0000305}.
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DR EMBL; M97496; AAA35915.1; -; mRNA.
DR EMBL; M95174; AAA58625.1; -; mRNA.
DR EMBL; X74322; CAC22258.1; -; Genomic_DNA.
DR EMBL; AC114492; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS465.1; -.
DR PIR; A46279; A46279.
DR RefSeq; NP_291031.2; NM_033553.2.
DR PDB; 1GNA; NMR; -; A=103-115.
DR PDB; 1GNB; NMR; -; A=103-115.
DR PDB; 1O8R; NMR; -; A=22-115.
DR PDBsum; 1GNA; -.
DR PDBsum; 1GNB; -.
DR PDBsum; 1O8R; -.
DR AlphaFoldDB; Q02747; -.
DR BMRB; Q02747; -.
DR SMR; Q02747; -.
DR BioGRID; 109235; 33.
DR IntAct; Q02747; 13.
DR STRING; 9606.ENSP00000349493; -.
DR BioMuta; GUCA2A; -.
DR DMDM; 290457645; -.
DR jPOST; Q02747; -.
DR MassIVE; Q02747; -.
DR PaxDb; Q02747; -.
DR PeptideAtlas; Q02747; -.
DR PRIDE; Q02747; -.
DR ProteomicsDB; 58118; -.
DR Antibodypedia; 2733; 180 antibodies from 21 providers.
DR DNASU; 2980; -.
DR Ensembl; ENST00000357001.3; ENSP00000349493.2; ENSG00000197273.4.
DR GeneID; 2980; -.
DR KEGG; hsa:2980; -.
DR MANE-Select; ENST00000357001.3; ENSP00000349493.2; NM_033553.3; NP_291031.2.
DR UCSC; uc001chd.2; human.
DR CTD; 2980; -.
DR DisGeNET; 2980; -.
DR GeneCards; GUCA2A; -.
DR HGNC; HGNC:4682; GUCA2A.
DR HPA; ENSG00000197273; Tissue enriched (intestine).
DR MIM; 139392; gene.
DR neXtProt; NX_Q02747; -.
DR OpenTargets; ENSG00000197273; -.
DR PharmGKB; PA29065; -.
DR VEuPathDB; HostDB:ENSG00000197273; -.
DR eggNOG; ENOG502S7QR; Eukaryota.
DR GeneTree; ENSGT00940000154436; -.
DR HOGENOM; CLU_166952_0_0_1; -.
DR InParanoid; Q02747; -.
DR OMA; CAEPMLP; -.
DR OrthoDB; 1552271at2759; -.
DR PhylomeDB; Q02747; -.
DR TreeFam; TF330731; -.
DR PathwayCommons; Q02747; -.
DR Reactome; R-HSA-8935690; Digestion.
DR SignaLink; Q02747; -.
DR SIGNOR; Q02747; -.
DR BioGRID-ORCS; 2980; 38 hits in 1056 CRISPR screens.
DR EvolutionaryTrace; Q02747; -.
DR GenomeRNAi; 2980; -.
DR Pharos; Q02747; Tbio.
DR PRO; PR:Q02747; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q02747; protein.
DR Bgee; ENSG00000197273; Expressed in ileal mucosa and 114 other tissues.
DR Genevisible; Q02747; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0030250; F:guanylate cyclase activator activity; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; NAS:UniProtKB.
DR Gene3D; 3.90.1450.10; -; 1.
DR InterPro; IPR000879; Guanylin.
DR InterPro; IPR036382; Guanylin_sf.
DR PANTHER; PTHR11318; PTHR11318; 1.
DR Pfam; PF02058; Guanylin; 1.
DR PIRSF; PIRSF001849; Guanylin; 1.
DR PRINTS; PR00774; GUANYLIN.
DR SUPFAM; SSF89890; SSF89890; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:8095028"
FT CHAIN 22..115
FT /note="HMW-guanylin"
FT /id="PRO_0000013135"
FT PEPTIDE 101..115
FT /note="Guanylin"
FT /id="PRO_0000013136"
FT DISULFID 69..82
FT /evidence="ECO:0000269|PubMed:12707255"
FT DISULFID 104..112
FT /evidence="ECO:0000269|PubMed:12707255"
FT DISULFID 107..115
FT /evidence="ECO:0000269|PubMed:12707255"
FT VARIANT 7
FT /note="S -> F (in dbSNP:rs2071499)"
FT /evidence="ECO:0000269|PubMed:1327879,
FT ECO:0000269|PubMed:1409606, ECO:0000269|PubMed:7892222"
FT /id="VAR_062678"
FT STRAND 23..31
FT /evidence="ECO:0007829|PDB:1O8R"
FT HELIX 34..37
FT /evidence="ECO:0007829|PDB:1O8R"
FT TURN 38..41
FT /evidence="ECO:0007829|PDB:1O8R"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1O8R"
FT HELIX 79..82
FT /evidence="ECO:0007829|PDB:1O8R"
FT HELIX 87..98
FT /evidence="ECO:0007829|PDB:1O8R"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:1GNA"
SQ SEQUENCE 115 AA; 12388 MW; C644DA910EED26FA CRC64;
MNAFLLSALC LLGAWAALAG GVTVQDGNFS FSLESVKKLK DLQEPQEPRV GKLRNFAPIP
GEPVVPILCS NPNFPEELKP LCKEPNAQEI LQRLEEIAED PGTCEICAYA ACTGC
